Syntarga Bv

Johannes Wilhelm Scheeren

Patrick Henry Beusker

Franciscus Marinus Hendrikus De Groot

Dick De Vos

Leonardus Wilhelmus Adriaan Van Berkom

Guuske Frederike Busscher

Carsten Albrecht

Antoinette Eugenie Seelen

Ralph Koekkoek

Franciscus Marinus De Groot

Leonardus Wilhelmus Van Berkom

This invention concerns multiple release spacers and spacer systems, which release multiple leaving groups following a single activation. It concerns compounds comprising a specifier linked to two or more of the same or different leaving groups (L in the figure) via a self-eliminating multiple release spacer or spacer system, which compounds upon a single activation step, in particular removal or transformation of the specifier, release at least two leaving groups. 

Prodrugs built as multiple self-elimination-release spacers

This invention is directed to prodrugs that can be activated at the preferred site of action in order to selectively deliver the corresponding therapeutic parent drugs to target cells or to the target site. This invention will therefore primarily but not exclusively relate to tumor cells as target cells. More specifically the prodrugs are compounds of the formula V&#x2014;(W)&#x2014;(X)&#x2014;A&#x2014;Z, wherein: V is a specifier; (W)&#x2014;(X)&#x2014;A is an elongated self-elimination spacer system; W and X are each a 1,(4+2n) electronic cascade spacer, being the same or different; A is either a spacer group of formula (Y)wherein: Y is a 1,(4+2n) electronic cascade spacer, or a group of formula U being a cyclization elimination spacer; Z is a therapeutic drug; k, l and m are integers from 0 (included) to 5 (included); n is an integer of 0 (included) to 10 (included), with the provisos that: &#x2014;when A is (Y): k+l+m&#x2267;1, and if k+l+m=1; &#x2014;when A is U: k+l&#x2267;1.

Elongated and multiple spacers in activatible prodrugs

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Malden, Netherlands

Johannes Wilhelm Scheeren